The Scientific Foundation of the Opioid Crisis: The Misuse of Evidence

• In Event: Medicaid and Drug Policy

Abstract

Background: Pharmaceutical marketing is widely regarded as a core driver of the opioid overdose epidemic. Pharmaceutical manufacturers, for example, contributed to the opioid crisis by targeting clinicians, promoting key opinion leaders, and shaping continuing medical education, health professional pain committees, advocacy organizations, and accreditation organizations. Similarly, shortcomings in the pharmaceutical supply chain, including insufficient monitoring, supervision, and risk mitigation on the part of pharmaceutical distributors, retailers, and the Food and Drug Administration (FDA) have been increasingly recognized as contributing to the crisis. However, less is understood about how pharmaceutical manufacturers, distributors, retailers, and consultants used scientific evidence to further their commercial interests and promote opioid sales. Misuse and misinterpretation of scientific evidence in the public domain, particularly to advance unsubstantiated claims that harm health, can undermine trust in democratic institutions. We used a novel collection of documents arising from opioid litigation to critically examine the scientific underpinning of five key, unsubstantiated opioid industry claims: 1) opioids are effective for chronic pain; 2) addiction is rare; 3) ‘pseudoaddiction’ is due to inadequate pain management; 4) no dose is too high; and 5) screening tools can predict addiction.

Methods: We identified pivotal scientific articles underlying the five claims commonly advanced by the opioid industry regarding opioid safety, effectiveness, and utilization. We used previously confidential corporate documents available at the Opioid Industry Documents Archive (OIDA) to extract, review, and categorize relevant documents to understand how each scientific article was used to advance each claim. We generated themes regarding industry’s use of scientific articles.

Results: We identified 15 scientific articles, published between 1982 and 2009, including letters to the editor, case reports, commentaries, original research, and reviews, supporting the five industry claims. Collectively mentioned by 3,666 documents in OIDA, the articles were included in a variety of materials, including training modules targeting pharmaceutical detailers and prescribers; knowledge brokering resources such as continued medical education activities; journal articles or textbooks; regulatory filings for new drug approvals, many without direct citations to the scientific articles but with inclusion in bibliographies; and emails such as correspondence with company sales force teams sharing strategies for how to incorporate the scientific articles into conversations with prescribers. Claims were advanced both deliberately and inadvertently and by a wide spectrum of actors, including industry, professional societies, and regulators. The scientific articles in OIDA sources were used to lend legitimacy to the claims, while substantive methodologic limitations as well as conflicts of interest, particularly among authors of the articles, were obscured.

Conclusions: The opioid industry promoted and extrapolated weak scientific evidence, often published by conflicted authors, to create uncertainty about the risks of prescription opioids, disarm criticism, and build credibility for their claims about their products’ benefits. In particular, they engaged in politics of expertise by selectively citing weak evidence to create the impression of scientific rigor. By doing so, opioid manufacturers influenced clinician behavior, public opinion, and key democratic institutions, including regulatory bodies and civic organizations, about the risks and benefits of opioids. The undermining of science and manufacturing of doubt about the risks of opioid products approved by U.S. regulatory bodies and prescribed by health care professionals licensed by government departments may further lead to democratic backsliding. Our findings have implications for clinicians who base clinical decisions on published studies and are members of professional societies, for policymakers who seek to regulate industries and establish guardrails around rent-seeking behavior from private actors to counteract democratic retrenchment, and for prevention of similar future public health crises.

Author

• Ravi Gupta, Johns Hopkins University